CN113164961A

CN113164961A - Piezoelectric micropipettor

Info

Publication number: CN113164961A
Application number: CN201980076642.0A
Authority: CN
Inventors: 萨博·巴林特
Original assignee: Cell Sorter Co ltd
Current assignee: Cell Sorter Co ltd
Priority date: 2019-02-15
Filing date: 2019-02-15
Publication date: 2021-07-23
Anticipated expiration: 2039-02-15
Also published as: JP2022524256A; CN113164961B; US20230027598A1; WO2020165617A1; EP3924107A1; JP7320864B2; EP3924107A4

Abstract

The invention relates to a piezoelectric micropipette comprising a capillary tube (1) forming a pipette, and an expansion chamber (2) connected to the capillary tube (1), the expansion chamber having a flexible element and being connected to a piezoelectric actuator (5). According to the invention, the flexible element (3) of the micropipette is arranged inside the expansion cavity (2), said flexible element being connected to a rigid displacement element (4), said piezoelectric actuator (5) being connected to said rigid displacement element (4).

Description

Piezoelectric micropipettor

Technical Field

The invention relates to a micropipette for accurately drawing or distributing a small amount of liquid sample, in particular to a micropipette based on a piezoelectric principle. In the analysis of liquid samples, in particular biological samples, it is often necessary to draw and dispense very small amounts of liquid in the nanoliter range, possibly to the nearest picoliter.

Further requirements are usually to remove small amounts of liquids, chemicals, biochemicals with high precision. Typical laboratory-used pipettes can be used to remove samples having volumes no less than about 0.1 microliters, but cannot reliably remove samples having volumes significantly less than this value. This is because the properties of microscopic droplets of 1 microliter or less are mainly dependent on the surface tension and its adhesion to the solid surface, unlike larger samples, which depend on the volume force. The capillary length of pure water at normal temperature and pressure is about 2 mm. This means that not gravity, but surface tension, is the decisive factor for the properties of the smaller water droplets. In addition to surface forces, evaporation of tiny droplets is also a problem. Water droplets with a volume below 1 microliter evaporate in a few minutes under laboratory conditions.

Background

Some microinjectors are currently available for very small injections. Such a microinjector, for example, an Eppendorf Femtojet microinjector, is capable of injecting liquids with a precision of femtoliter by means of a micropipette. In the microinjector, a steady, very slow flow of liquid is generated and the volume of liquid injected is adjusted by the injection time. However, these solutions are not suitable for drawing and continuously dispensing very small samples in the picoliter and subpicoliter ranges. This is because continuous drawing and injection of samples can only be performed with significant lag. Because whole liquid system's volume is very big, and elasticity such as pipeline delimit the device and can take place the inflation, and the sealing member will be unable when reversing the liquid flow direction, keeps carrying out the regulation of high accuracy to the volume. Above the microliter range this is not a problem, but in the nanoliter range it poses a serious technical hurdle.

In automated sampling and dispensing systems, a controllable pipette is used. These pipettors are capable of drawing different volumes of liquid depending on the construction and operating principle.

With certain controllable pipettors, the volume change required to draw and dispense the sample is achieved by moving a piston in the syringe. According to U.S. patent No. 7,125,727, a metering piston moved by a piezoelectric actuator is used to control the flow of liquid in the needle. However, the typical stroke (maximum longitudinal deformation) of a piezoelectric actuator is only a few microns. To improve dispensing accuracy, it is preferred to use a smaller diameter cartridge. However, for practical reasons, the diameter of the barrel (and the piston) cannot be below the millimeter level. In addition, a seal must be employed between the piston surface and the barrel. The seal is typically made of an elastomeric material and is therefore easily deformable. Typically, the volume change resulting from deformation of a seal having dimensions in the millimeter range is comparable to the volume change resulting from movement of the piston in the micrometer or smaller range. Such volume changes greatly reduce the accuracy of liquid removal. The amount of liquid drawn in the range of picoliters and below picoliters can only be determined with very low accuracy based on the position of the piston. The piston or cylinder must slide along the resilient seal. The accuracy of the piezoelectric actuator can be used for the movement of the piston, but not in the nanometer range. In the case of such a small relative displacement of the piston, the moving surface (presumably) does not slide, but rather the seal is deformed, because of the high coefficient of adhesive friction of the seal. It is not possible to determine how much sliding displacement between the seal and the contact surface will occur. This severely reduces the accuracy of the liquid treatment. In principle, the accuracy of the liquid removal can be improved by using a so-called hamilton-specific syringe instead of a conventional piston. In this case, a high-precision teflon piston is also used as a seal. However, when the moving direction is changed, even in the hamilton syringe, the accuracy of removing the liquid in the picoliter range is low.

In another known device, the side of the expansion chamber connected to the pipette terminates with a septum, or one of the side walls is configured as a septum. Such a piezo-electric based micropipette is described in U.S. patent No. 7125519. In this device, the capillary tube of the micropipette is connected to an expansion chamber, the wall of which is configured as a septum, through a liquid channel. The outer surface of the diaphragm is provided with a piezoelectric element, and when a voltage is applied to the piezoelectric element, the size of the piezoelectric element changes, thereby changing the form of the diaphragm. As the morphology of the membrane changes, the volume of the expansion chamber changes, which results in aspiration or injection of the liquid. The amount of liquid sucked or injected depends on the size of the expansion chamber and the deformation of the membrane or, more precisely, on the volume change of the expansion chamber.

One of the disadvantages of this device is that it cannot be disassembled because its parts are glued together. Thus, filling the device with liquid and cleaning the device between two successive applications can be quite cumbersome. The device should be disposable for removal of reagents that may contaminate the interior of the device. If the device is filled with air, the accuracy of liquid removal will be rather low due to the compressibility of air and the high laplace pressure (due to the presence of surface tension) over a small cross section of the pipette tip.

Disclosure of Invention

In the creation of the present invention we start with a micropipette based on the piezoelectric principle, comprising a capillary tube forming the pipette, and an expansion chamber connected to said capillary tube, said expansion chamber having a flexible element and being connected to a piezoelectric actuator.

According to the invention, the drawbacks of the prior art can be eliminated by the following solution: a piezoelectric micropipette having a flexible element disposed within the expansion cavity, the flexible element being connected to a rigid displacement element, the piezoelectric actuator being connected to the rigid displacement element. By this arrangement, any small expansion chamber can be (practically) formed in which a correspondingly small volume (e.g. in the nanoliter range) of liquid sample can be drawn and dispensed by a suitably small displacement of the rigid displacement member.

According to one aspect of the invention, the expansion chamber is substantially cylindrical, the flexible element disposed within the expansion chamber is configured as an O-ring, and the rigid displacement element is configured as a substantially disc-shaped pressure plate. In such an arrangement, the expansion chamber (e.g. the amount of liquid that can be drawn or dispensed) and the accuracy of the dispensing will in fact be determined by the dimensions of the O-ring.

The O-ring disposed in the expansion chamber may be an optionally replaceable O-ring having a size selected from a range of sizes between a minimum size and a maximum size, wherein the cylindrical expansion chamber is configured to accommodate O-rings of different sizes and the inner diameter of the cylindrical side wall of the expansion chamber substantially corresponds to the outer diameter of the maximum O-ring.

The surface of the cylindrical expansion chamber in contact with the O-ring is a substantially planar surface with concentric grooves for concentrically locating O-rings of different sizes.

According to the present invention, a capillary tube forming a micropipette is detachably attached to an expansion chamber, wherein a capillary hole is formed in a pipette holder for connecting the capillary tube to the expansion chamber.

According to another preferred embodiment of the invention, the expansion chamber is provided in a rigid housing forming a pipette holder, which housing may be closed by a removable closure.

In this embodiment, the enclosure is formed by a housing that houses the piezoelectric actuator and provides it with an internal space.

In another preferred embodiment, a closure of a micropipette holder is configured to enable filling of the micropipette with an inlet connection element.

A micropipette according to the invention is preferably provided, in which the capillary tube forming the pipette is fixed to the pipette holder with a detachable fixing element (for example a threaded fixing element).

The pipette holder has a corresponding receiving space formed therein for receiving a capillary tube forming a pipette. In the pipette holder, a receiving chamber for receiving a capillary tube forming a pipette is also provided with a sealing and/or fixing element between the capillary tube and the receiving chamber.

According to a further aspect of the invention, in a receiving chamber in the pipette holder for receiving a capillary tube forming a pipette, one of the sealing and/or securing elements is preferably tapered, and the remaining sealing and/or securing elements are preferably configured as O-rings.

In this configuration, in a receiving cavity in the pipette holder for receiving a capillary tube forming a pipette, a guide sleeve for gripping and guiding the capillary tube is provided between the conical seal and the O-ring.

In a containing cavity for containing a capillary tube forming a pipette in a pipette bracket, a guide sleeve for clamping and guiding the capillary tube is arranged between the conical sealing piece and the O-shaped ring, the tail section of the guide sleeve is close to the conical sealing piece, is conical and corresponds to the conical shape of the conical sealing piece; the end face of which is adjacent to the O-ring and has an at least partially planar surface and is substantially perpendicular to the longitudinal direction.

According to a further embodiment of the invention, the pipette fixing element has an illumination device, preferably an LED illumination device, which is capable of illuminating the pipette tip.

The lighting device may have a support plate configured as a circular disk with LED lighting elements arranged in at least one concentric circle.

The LED lighting elements in the lighting device are preferably arranged and configured to be able to provide phase contrast lighting.

Description of the drawings:

FIG. 1 is a side view of a piezoelectric micropipette according to one aspect of the present invention;

FIG. 2 is a cross-sectional side view of the piezoelectric micropipette shown in FIG. 1;

fig. 3 is a bottom view of the piezoelectric micropipette with illumination shown in fig. 1;

FIG. 4 is a side view of a piezoelectric micropipette with a fill inlet connection element;

FIG. 5 is a cross-sectional side view of a piezoelectric micropipette with a fill inlet connection element as shown in FIG. 4;

fig. 6 is a cross-sectional side view of a piezoelectric micropipette with the pipette tip illuminated by an illumination element;

fig. 7 is a cross-sectional side view of a piezoelectric micropipette with a fill inlet connection element and a pipette tip illuminated by an illumination element;

fig. 8 is an enlarged view of an expansion cavity and surrounding elements of a micropipette according to the present invention;

fig. 9 is an enlarged view of a pipette holder and associated components of a piezoelectric micropipette.

Detailed Description

Fig. 1 is a side view of a piezoelectric micropipette according to one aspect of the present invention, having a capillary 1 forming the pipette, a housing 6 for housing a piezoelectric actuation element, a pipette holder 7, a threaded securing element 12, a support plate 13, and a shroud 11. The front face of the housing 6 is provided with a fixing face 16 with a fixing screw 18. In this embodiment, a spring 14 is provided between the fixing member 12 and the support plate 13. The spring 14 presses the support plate 13 containing the LED lighting elements downwards. In this way, the lighting element remains stable in the vertical position. The support plate 13 is fixed by a threaded nut and also serves to adjust the height of the lighting panel. The spring thus presses the retainer plate 13 against the nut.

The mounting surface 16 may be used to mount the piezoelectric micropipette of the present invention on a robotic arm that is movable along at least one coordinate and allows the piezoelectric micropipette to be moved programmatically in the space between desired locations, thereby enabling the system to be configured and used for automated pipetting.

Fig. 2 shows a cross-sectional side view of the piezoelectric micropipette shown in fig. 1. As can be seen, the upper end of the capillary tube 1 is arranged in a pipette holder 7. The pipette holder 7 is formed with a capillary hole 1a coaxial with the capillary tube 1, and the capillary hole 1a communicates with the preferably cylindrical expansion chamber 2. In the expansion chamber 2 a flexible element 3 in the form of an O-ring is arranged, the flexible element 3 being in mechanical contact with a rigid displacement element 4 made in the form of a pressure plate or a circular plate/disc. The rigid displacement element 4 is connected to a piezoelectric actuator 5, the piezoelectric actuator 5 being arranged in a housing 6. The housing 6 is mechanically connected to a pipette holder 7. To establish the mechanical connection, the housing 6 has an internal thread and the pipette holder 7 has an external thread.

The expansion chamber 2 is thus terminated with the upper end face of the pipette holder 7, the O-ring 3 mounted in the expansion chamber 2, the rigid displacement element 4. The dimensions of the O-ring 3 provided in the expansion chamber 2 may be selected in a range of dimensions between a minimum dimension and a maximum dimension. Furthermore, the O-ring may be replaced if necessary. The cylindrical expansion chamber 2 is preferably configured to accommodate O-rings 3 of different sizes, wherein the inner diameter of the cylindrical side wall of the expansion chamber 2 corresponds to the outer diameter of the largest O-ring 3 that can be selected.

The expansion chamber 2 is a cylindrical recess formed in the upper end of the pipette holder 7 for receiving the O-ring 3 and has a generally planar O-ring 3 contact surface.

In a preferred embodiment of the micropipette of the present invention, concentric grooves (not shown) are provided in the expansion chamber 2 on the contact surface of the substantially planar O-ring 3 for concentrically positioning O-rings 3 of different sizes.

The upper end of the capillary tube 1 can be inserted and set into a cylindrical receiving space of the pipette holder 7. In order to enable correct positioning of the capillary 1, upper and lower sealing and/or fixing

elements

8 and 9 are inserted and arranged in the receiving chamber. As shown in fig. 2, the upper end of the capillary tube 1 may be provided with a conical seal 8. The conical seal has a planar upper end surface in contact with a generally planar contact surface at the upper end of the cylindrical receiving chamber and a lower conical outer surface in contact with a conical inner surface at the upper end of a guide sleeve 10 for guiding the capillary 1. The conical outer contact surface of the lower end of the conical seal 8 tapers downwardly and the conical inner contact surface of the guide sleeve 10 widens correspondingly upwardly. The conical seal 8 has a similar cone angle to the conical end face of the guide sleeve 10. The conical seal 8 is used for sealing, fixing and positioning the upper end of the capillary tube 1 coaxially with the capillary hole 1a of the pipette holder 7 with high precision. The lower end of the guide sleeve 10 terminates with a plane substantially perpendicular to the longitudinal direction and is in contact with a lower sealing and fixing element configured as an O-ring 9. The O-ring 9 is fixed by a fixed holding element 12 detachably connected to the pipette holder 7 for pressing the O-ring 9 against the planar end face of the guide sleeve 10. The fixed holding element 12 is preferably a threaded component, in the embodiment shown the fixed holding element 12 having an external thread for connecting an internal threaded portion at the lower end of the pipette holder 7. The fixed retaining element 12 has an upper threaded portion, a lower threaded portion, and an intermediate portion extending in a cross direction. The lower threaded portion can accommodate a tray 13 for carrying the lighting device.

The piezoelectric actuator 5 may be disposed in a receiving cavity of the housing 6, and the housing 6 may be detachably connected to the pipette holder 7. To this end, the housing may have an internally threaded portion and may act as a closure. The piezo-electric actuator 5 may be supplied with a direct current control voltage, when the piezo-electric actuator is caused to compress or expand in the longitudinal direction. The control voltage for the piezo actuator 5 can be introduced through an opening in the housing 6 hood 11 with a voltage supply cable, not shown. Due to the change in the longitudinal dimension of the piezoelectric actuator 5, the O-ring 3 located in the expansion chamber 2 will be compressed to a different extent, resulting in a change in the volume of the expansion chamber 2. On the other hand, the volume change of the expansion chamber 2 will cause the liquid in the capillary 1 and the capillary hole 1a to be drawn or released.

Fig. 3 shows an illumination device, which may preferably be an LED illumination device, for use with the piezoelectric micropipette of the present invention. As shown in fig. 3, the lighting device has a preferably circular carrier 13, the carrier 13 having LED lighting elements 15 arranged in at least one concentric circle. The LED illumination element 15 provides suitable illumination for the pipette tip, which may be advantageous, in particular when taking microscopic images. In certain applications, it may be advantageous to provide and configure an LED lighting element 15 capable of providing phase contrast illumination. As shown, the LED lighting elements 15 are arranged in four (two pairs) of predetermined concentric circles of different sizes.

In the present embodiment, the pipette holder 7 of the micropipette is detachably connected to the housing 6 accommodating the piezoelectric actuator 5 in the form of a screw connection, and therefore the housing 6 may be detached and replaced with a closure 20 connected to the pipette holder 7 by a screw portion, as shown in fig. 4 and 5. The upper end of the threaded closure 20 is provided with a filling inlet 21, which filling inlet 21 can be connected to a standard syringe or the like for filling a micropipette with liquid. Accurate operation of a micropipette requires that the entire interior space of the micropipette be filled with liquid and bubble free. Because the gas is compressible, the resulting trapped air bubbles can reduce the dispensing accuracy of the micropipette. During filling of the present micropipette, the O-ring 3 in the expansion chamber 2 is replaced with another O-ring 22 for filling purposes. A filling head consisting of a closure 20 and a filling inlet 21 is only required for filling and finally for a washing process in connection with a micropipette. Before a new (dry) micropipette without any liquid is used for the first time, the micropipette must be completely filled with a liquid suitable for the sampling procedure (e.g. water) and free of air bubbles by means of a filling head. After the sampling procedure is completed, the micropipette is preferably emptied and rinsed, and the wash solution is emptied. Because the components of the micropipette of the present invention are designed to be removable, individual components may be individually cleaned, sterilized, or simply replaced.

Fig. 6 and 7 show light beams emitted by the illumination device of a micropipette of the present invention. Fig. 3 shows a bottom view of the LED lighting elements 15, said LED lighting elements 15 being arranged in four concentric circles, such that each circle of LED lighting elements 15 defines a predetermined cone angle with the tip of the capillary 1. The taper angles of the inner and outer circles of a pair of circles in the illustrated embodiment are 15 degrees and 30 degrees, respectively. The diameters of the concentric circles are determined such that the light beams of the inner and outer LED lighting elements 15 of one pair of circles intersect at the tip of the capillary 1, and the light beams of the inner and outer LED lighting elements 15 of the other pair of circles intersect at a position spaced apart from the tip of the capillary 1 by a predetermined distance. The predetermined distance in the embodiment shown is 20 mm. This arrangement is necessary for phase contrast microscopy of a sample at or 20mm below the tip of the capillary 1.

The function of the piezoelectric micropipette of the present invention will now be described in more detail with reference to fig. 8. Fig. 8 depicts in an enlarged view the expansion chamber 2, the O-ring 3, the pressure plate 4 and the piezo actuator 5. The mathematical formula for calculating the volume of liquid that can be removed using the piezoelectric micropipette of the present invention will now be provided.

The calculation was performed under the condition that the size of the O-ring was 1X 1mm, which is one of the smallest sizes on the market. As the calculations demonstrate, the highest dispensing accuracy can be achieved with the smallest size O-ring to displace the smallest amount of liquid, and with the piezoelectric actuator having the smallest travel distance or stroke.

With O-rings terminating with two parallel plates, the closed volume is calculated as follows:

v ═ (D/2+ D/2)2 × pi × H ≈ pi mm3 ≈ 3.14 μ l.

Wherein D is 1mm (opening diameter of O-shaped ring)

d is 1mm (thickness of O-shaped ring)

H1 mm (thickness of O-shaped ring)

However, the volume V also comprises half of the volume of the O-ring, since the volume of the cylindrical space between the two plates in the range of the contact line of the O-ring is calculated. Volume of O-ring (ring):

v 2 × pi 2 × D/2 × (D/2)2 ═ pi 2/4. mu.l

And finally obtaining the volume of the liquid sealed by the O-shaped ring: V-V/2 π - (π 2)/8 ≈ 1.9mm3 (microliters)

Thus, the volume of liquid enclosed within the expansion chamber 2 is 1.9 microliters, or about 2 microliters.

Under the condition that the volume of the O-shaped ring is unchanged and the compression deformation is symmetrical, the change of the liquid volume is as follows:

Δ hx (D/2+ D/2)2 × pi ═ Δ H × pi (microliters)

The maximum longitudinal movement (Δ H _ max) of the piezoelectric element used in this example was 5 μm with an accuracy of about 1 nm. Thus, the piezoelectric element is able to displace about 15 nanoliters of liquid. The dispensing accuracy was about 3 picoliters.

When a piezoelectric element with a small stroke is used, the maximum displacement amount is reduced, and the distribution precision is improved. Dispensing accuracies of 0.1 nm and even higher can be achieved with piezoelectric elements. When the O-ring is used, the accuracy is 0.3 picoliter.

In the present example, to avoid hysteresis due to polarity inversion, it is preferred to use a piezoelectric element having a dc control and a unipolar control circuit. Even in this case, the voltage-displacement curve of the piezoelectric element is not completely linear, and thus may need to be calibrated in advance. In the practical application of the invention, we use

P882 and P888 piezoelectric elements.

The piezoelectric micropipettor has the main advantages of capability of electrical control, high speed, simple structure and high cost benefit. The micropipette of the present invention can be used for both transmitted light imaging and reflected light imaging, and in practice can be used for inverted microscopes. The invention is also suitable for microscopic imaging under the condition that the optical axis is coaxial with the axis of the micropipettor. The micropipette surface that comes into contact with the liquid sample is made entirely of inert materials: the capillary tube is made of glass and the liquid transfer device is supportedThe frame, expansion chamber and pressure plate are made of stainless steel or plastic, and the O-ring and conical seal are made of rubber or

(polytetrafluoroethylene).

Reference numerals

1 capillary tube (micropipettor)

1a capillary hole

2 expansion chamber

3O-shaped ring

4 rigid displacement member, pressure plate

5 piezoelectric actuator

6 piezoelectric actuator casing, closure

7 pipettor support

8 conical seal

9O-shaped ring

10 guide sleeve

11 protective cover

12 (screw thread) holding element

13 supporting plate

14 spring

15 LED lighting element

16 fixed surface

17 sink

18 screw

20 closure

21 filling inlet

22O-shaped ring

Claims

1. A piezoelectric micropipette comprising a capillary tube (1) forming a pipette, and an expansion chamber (2) connected to the capillary tube (1), the expansion chamber having a flexible element and being connected to a piezoelectric actuator (5), characterized in that the flexible element is a flexible element (3) arranged within the expansion chamber (2), the flexible element being connected to a rigid displacement element (4), the piezoelectric actuator (5) being connected to the rigid displacement element (4).

2. The micropipette according to claim 1, wherein the expansion chamber (2) is substantially cylindrical, the flexible element arranged therein being configured as an O-ring (3), and the rigid displacement element (4) being configured as a substantially disc-shaped pressure plate.

3. The micropipette according to claim 2, characterized in that the O-ring (3) arranged in the expansion chamber (2) is an optionally exchangeable O-ring (3) of a size that can be selected from a range of sizes between a minimum size and a maximum size, wherein the cylindrical expansion chamber (2) is configured to accommodate O-rings (3) of different sizes, and wherein the inner diameter of the cylindrical side wall of the expansion chamber substantially corresponds to the outer diameter of the maximum O-ring (3).

4. A micropipette according to claim 3, wherein the surface of the cylindrical expansion chamber (2) in contact with the O-ring (3) is a substantially planar surface.

5. A micropipette according to claim 3, wherein the surface of the cylindrical expansion chamber (2) in contact with the O-ring (3) is provided with concentric grooves for concentrically positioning the O-ring (3).

6. The micropipette according to any one of claims 1-5, characterized in that a pipette-forming capillary tube (1) is detachably connected to the expansion chamber (2) by means of a pipette holder (7), wherein a capillary hole (1a) is formed in the pipette holder for connecting the capillary tube (1) with the expansion chamber (2).

7. The micropipette according to any one of claims 1-6, characterized in that the expansion chamber (2) is arranged in a rigid housing forming a pipette holder (7), which housing can be closed by a detachably connected closure (6).

8. The micropipette according to claim 7, characterized in that the closure (6) is formed by a housing which accommodates the piezoelectric actuator (5) and has a cavity for accommodating the piezoelectric actuator (5).

9. The micropipette according to claim 7, wherein the closure (20) is configured for filling a micropipette and has an inlet connection element (21).

10. The micropipette according to any one of claims 1-9, characterized in that the pipette-forming capillary tube (1) is fixed to the pipette holder (7) with a detachable fixing element, preferably a threaded fixing element (12).

11. The micropipette according to claim 10, wherein a receiving cavity is formed in the pipette holder (7) for receiving a capillary tube (1) forming a pipette.

12. The micropipette according to claim 11, characterized in that in the pipette holder (7) the receiving cavity for receiving a capillary tube (1) forming a pipette is further provided with at least one sealing and/or fixing element (8, 9) between the capillary tube (1) and the receiving cavity wall.

13. The micropipette according to claim 12, wherein in a receiving cavity in a pipette holder for receiving a capillary tube (1) forming a pipette, one of the sealing and/or fixing elements is a conical sealing and/or fixing element (8), the remaining sealing and/or fixing elements being configured as O-rings (9).

14. The micropipette according to claim 13, characterized in that in the pipette holder (7) the receiving chamber (2) for receiving a capillary tube (1) forming the pipette is further provided with a guide sleeve (10) between the conical seal (8) and the O-ring (9) for fixing and guiding the capillary tube (1).

15. The micropipette according to claim 13, characterized in that in a receiving cavity (2) in the pipette holder for receiving a capillary tube (1) forming a pipette, a guide sleeve (10) for clamping and guiding the capillary tube between the conical seal (8) and the O-ring (9) has an end section close to the conical seal (8), is conical in shape and corresponds to the conical shape of the conical seal (8); the end face of which is adjacent to the O-ring (9) and has an at least partly planar surface and is substantially perpendicular to the longitudinal direction.

16. The micropipette according to any one of claims 1-15, wherein the illumination device is connected to a pipette fixed holding element (12).

17. The micropipette of claim 16, wherein the illumination device is an LED illumination device.

18. The micropipette according to claim 17, wherein the illumination device has a circular carrier plate (13), the carrier plate (13) having LED illumination elements (15) arranged in at least one concentric circle.

19. The micropipette of claim 18, wherein the LED illumination element (15) in the illumination device is arranged and configured to be capable of providing phase contrast illumination.

20. The micropipette of any one of claims 1-19, wherein the micropipette is mounted on a robotic arm that enables the micropipette to be programmed between desired spatial positions.